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Background: Viral respiratory infections are one of the main causes of hospitalization in children. Even if mortality rate is low, 2% to 3% of the hospitalized children need mechanical ventilation. Risk factors for admission to the pediatric intensive care unit (PICU) are well known, while few studies have described risk factors for invasive ventilator support and prolonged hospitalization. Methods: A retrospective study including all patients aged between 2 and 18 months with a confirmed viral respiratory infection, requiring admission to PICU from September to March between 2015 and 2019, was conducted at Bambino Gesù Children's Hospital in Rome, Italy. Results: One hundred ninety patients were enrolled, with a median age of 2.7 months; 32.1% had at least one comorbidity, mainly prematurity. The most frequent isolated viruses were RSV‐B, rhinovirus, and RSV‐A; 38.4% needed mechanical ventilation. This subgroup of patients had lower median birth weight compared with patients not requiring mechanical ventilation (2800 g vs. 3180 g, p = 0.02); moreover, comorbidities were present in 43.8% of intubated patients and in 24.8% of patients treated with non‐invasive ventilation (p = 0.006). Viral coinfection did not result to be a risk factor for mechanical support, while virus–bacteria coinfection was significantly associated with mechanical ventilation (p < 0.001). Similar risk factors were identified for prolonged hospitalization. Conclusions: Early identification of patients who could have a sudden respiratory deterioration and need of mechanical ventilation is crucial to reduce complications due to orotracheal intubation and prolonged hospitalization in PICU. Further studies are needed to define high‐risk group of patients and to design targeted interventions. [ABSTRACT FROM AUTHOR]

Aim: To understand the variations in practice for caffeine use among neonatal units in the United Kingdom., Methods: An online survey was sent to every neonatal unit in the United Kingdom., Results: We received a response from 92 neonatal units (47%) with the proportion of response from special care, Local neonatal units, neonatal intensive care units and neonatal surgical units were 23%, 34%, 23% and 21% respectively. All the units reported the use of caffeine, and 40 units (46%) initiated caffeine within 24 h of birth. Fifty-nine units (64%) reported routine use of caffeine for pre-term infants <32 weeks. Seventy-one units (77%) reported that they continue caffeine for infants needing mechanical ventilation. Thirty-one units (34%) discontinued caffeine at 34 weeks post-menstrual age, irrespective of the respiratory support. Ten units (11%) reported discontinuation of caffeine only after weaning off all respiratory support, and 40% of units had a variable practice of discontinuing caffeine depending on the individual baby. Seventy-nine units (86%) reported they would regularly optimise caffeine dose based on weight checks., Conclusion: Our survey showed some variation in practice with regards to the timing of caffeine initiation, gestational age cut-off for routine caffeine prescription and discontinuation., (© 2022 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: The aim of this review was to give an overview of available data on end-tidal CO 2 (etCO 2 ) monitoring, also called capnometry, during neonatal transport., Methods: Pubmed/MEDLINE database was searched using research question (capno* OR etCO2 OR detCO2 OR (['end tidal' OR 'end-tidal'] AND [CO2 OR 'carbon dioxide']) AND (neonat* OR infant* OR newborn*) AND transport*). All articles relevant to the topic were reviewed and summarised., Results: The lack of studies relevant to neonatal transport prompted us to extend the search to capnometry in a neonatal intensive care setting. The published studies are showing conflicting results. The different study populations, technologies used to measure etCO 2 , types of etCO 2 sampling and the diverse sites of blood gas tests make the data unsuitable for systematic comparison., Conclusion: Further research to obtain more data on capnometry during neonatal transport will be necessary to define precisely under what circumstances can end-tidal monitoring of CO 2 be reliably used in neonates during transport and also how to interpret the measured values., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aim: To study if stabilisation using a new respiratory support system with nasal prongs compared to T-piece with a face mask is associated with less need for mechanical ventilation and bronchopulmonary dysplasia., Methods: A single-centre follow-up study of neonates born <28 weeks gestation at Karolinska University Hospital, Stockholm included in the multicentre Comparison of Respiratory Support after Delivery (CORSAD) trial and randomised to initial respiratory support with the new system versus T-piece. Data on respiratory support, neonatal morbidities and mortality were collected up to 36 weeks post-menstrual age., Results: Ninety-four infants, 51 female, with a median (range) gestational age of 25 + 2 (23 + 0, 27 + 6) weeks and days, were included. Significantly fewer infants in the new system group received mechanical ventilation during the first 72 h, 24 (52.2%) compared with 35 (72.9%) (p = 0.034) and during the first 7 days, 29 (63.0%) compared with 39 (81.3%) (p = 0.045) in the T-piece group. At 36 weeks post-menstrual age, 13 (28.3%) in the new system and 13 (27.1%) in the T-piece group were diagnosed with bronchopulmonary dysplasia., Conclusion: Stabilisation with the new system was associated with less need for mechanical ventilation during the first week of life. No significant difference was seen in the outcome of bronchopulmonary dysplasia., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aims: This study aimed to evaluate the efficacy and safety of regdanvimab, an anti-SARS-COV-2 monoclonal antibody approved by the European Medicines Agency in November 2021, for the treatment of confirmed COVID-19 disease., Methods: Cochrane Library, PubMed, medRxiv and Google Scholar were searched for relevant evidence up to October 27, 2022. The quality of included studies was assessed using the Cochrane risk of bias tools. Data were analysed using RevMan software., Results: Eight studies involving 4793 patients were included. A significant difference was observed between the regdanvimab and no-regdanvimab groups in terms of length of hospital stay (mean difference [MD] = -1.15, 95% confidence interval [CI]: -1.80 to -0.43), clinical recovery (odds ratio [OR] = 2.09, 95% CI: 1.38 to 3.18), disease progression (OR = 0.23, 95% CI: 0.16 to 0.33), the need for oxygen therapy (OR = 0.33, 95% CI: 0.25 to 0.43) and duration of oxygen therapy (MD = -3.00, 95% CI: -4.44 to -1.56). However, no significant difference was detected between 2 groups regarding mortality rate (OR = 0.46, 95% CI: 0.11 to 1.89), need for mechanical ventilation (OR = 0.39, 95% CI: 0.08 to 1.89) and hospital admission rate (OR = 0.61, 95% CI: 0.35 to 1.03). The incidence of adverse events was similar in both groups (OR = 0.96, 95% CI: 0.77 to 1.18)., Conclusion: Regdanvimab was not effective in reducing mortality and hospital admission rate in patients with mild to moderate COVID-19, but it was effective in improving other efficacy outcomes. Further research is needed to confirm these findings., (© 2023 British Pharmacological Society.)

Aim: We evaluated the predictive ability of prolonged requirements for mechanical ventilation or tube feeding support for 18-month composite outcomes in infants with hypoxic-ischaemic encephalopathy treated with hypothermia., Methods: This retrospective, nationwide, observational study focused on newborn infants registered in Japan's Baby Cooling Registry between 1 January 2012 and 31 December 2016. The adverse outcomes were defined as death or survival with cerebral palsy, visual or auditory impairment or the requirement for mechanical ventilation or tube feeding at 18 months of age., Results: Adverse outcomes occurred in 165 (28%) of the 591 children in the final cohort. These were predicted by prolonged dependence on mechanical ventilation or tube feeding for more than seven and more than 14 days. The respective values were positive predictive value 0.34 (95% CI 0.33-0.34) and 0.60 (95% CI 0.56-0.62), negative predictive value 0.97 (95% CI 0.91-0.99) and 0.93 (95% CI 0.90-0.95) and area under the curve 0.59 (95% CI 0.54-0.64) and 0.81 (95% CI 0.77-0.85)., Conclusion: Prolonged dependence on mechanical ventilation or tube feeding for more than 14 days may be useful in predicting 18-month outcomes in newborn infants who have received therapeutic hypothermia., (© 2023 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

New Findings: What is the central question of this study? What is the effect of lowering the normally occurring work of breathing on the electrical activity and pressure generated by the diaphragm during submaximal exercise in healthy humans? What is the main finding and its importance? Ventilatory assist during exercise elicits a proportional lowering of both the work performed by the diaphragm and diaphragm electrical activity. These findings have implications for exercise training studies using proportional assist ventilation to reduce diaphragm work in patients with cardiopulmonary disease., Abstract: We hypothesized that when a proportional assist ventilator (PAV) is applied in order to reduce the pressure generated by the diaphragm, there would be a corresponding reduction in electrical activity of the diaphragm. Healthy participants (five male and four female) completed an incremental cycle exercise test to exhaustion in order to calculate workloads for subsequent trials. On the experimental day, participants performed submaximal cycling, and three levels of assisted ventilation were applied (low, medium and high). Ventilatory parameters, pulmonary pressures and EMG of the diaphragm (EMG di ) were obtained. To compare the PAV conditions with spontaneous breathing intervals, ANOVA procedures were used, and significant effects were evaluated with a Tukey-Kramer test. Significance was set at P < 0.05. The work of breathing was not different between the lowest level of unloading and spontaneous breathing (P = 0.151) but was significantly lower during medium (25%, P = 0.02) and high (36%, P < 0.001) levels of PAV. The pressure-time product of the diaphragm (PTP di ) was lower across PAV unloading conditions (P < 0.05). The EMG di was significantly lower in medium and high PAV conditions (P = 0.035 and P < 0.001, respectively). The mean reductions of EMG di with PAV unloading were 14, 22 and 39%, respectively. The change in EMG di for a given lowering of PTP di with the PAV was significantly correlated (r = 0.61, P = 0.01). Ventilatory assist during exercise elicits a reduction in the electrical activity of the diaphragm, and there is a proportional lowering of the work of breathing. Our findings have implications for exercise training studies using assisted ventilation to reduce diaphragm work in patients with cardiopulmonary disease., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Aim: To determine if the use of closed-loop automated oxygen control (CLAC) reduced the incidence and duration of hypoxemic episodes (SpO 2  < 92%) in ventilated infants born at or above 34 weeks of gestation., Methods: Infants were studied on two consecutive days for 6 h each day. They were randomised to receive standard care (manual oxygen control) or standard care with a CLAC system (automated oxygen control) first., Results: Sixteen infants with a median (IQR) gestational age of 37.4 (36.6-38.8) weeks were studied at a median (IQR) postmenstrual age of 38.8 (37.4-39.8) weeks. During the automated oxygen control period, infants spent less time in hypoxemia (SpO 2  < 92%) (p = 0.033), episodes of desaturation were shorter (p = 0.001), the time spent within target SpO 2 range (92%-96%) was increased (p = 0.001), and the FiO 2 delivery was lower (p = 0.018). The time spent in hyperoxemia (SpO 2  > 96%) was reduced during automated oxygen control (p = 0.011), the episodes of hyperoxemia were of shorter duration (p = 0.008) and fewer manual adjustments were made to the FiO 2 (p = 0.005)., Conclusions: Closed-loop automated oxygen control in ventilated infants born at or near term was associated with a reduction in the incidence and duration of hypoxemic episodes with more time spent in the target oxygen range., (© 2022 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aims: The mortality of critically ill patients undergoing mechanical ventilation (MV) is high and few strategies are available. We explored the relationship between ondansetron pre-treatment, the neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR), and mortality of ventilated patients in the intensive care unit., Methods: We developed a retrospective cohort study that involved patients undergoing MV in the Multiparameter Intelligent Monitoring in Intensive Care IV (MIMIC-IV) database. Causal mediation analysis was conducted to assess the relationship of ondansetron use and mortality and to explore the potential causal pathway mediated by the NLR or PLR. The primary outcome was 28-day mortality., Results: A total of 17 927 eligible patients took part in the study (5665 had taken ondansetron before MV initiation and 12 262 patients had not). The odds ratio (OR) for 28-day mortality for ondansetron use uncorrelated with the mediator (NLR, PLR) was 0.72 (95% confidence interval [CI] = 0.64-0.81, P < .001). Ondansetron was also associated with a reduction in 28-day mortality after controlling for the mediator of NLR (OR = 0.98, 95% CI = 0.97-0.99, P < .01). For the indirect effect, the NLR could explain 13.47% (95% CI = 8.59-20.54%, P < .01) of the impact of ondansetron use on 28-day mortality. The proportion mediated increased to 21.50% (95% CI = 12.36-47.44%, P < .01) for 90-day mortality. Adjusted mediation analysis revealed no suggestion of a causal mediation pathway for this effect by the PLR (P = .12)., Conclusions: NLR may play substantial roles in the relationship between ondansetron pre-treatment before initiation of mechanical ventilation and the reduction of death risk in ventilated patients., (© 2021 British Pharmacological Society.)

Aims: Type 1 interferon (IFN) is used to treat patients with coronavirus disease-2019 (COVID-19) but robust supporting evidence is lacking. We investigated the association between IFN-α-2b and the clinical outcomes of patients with COVID-19., Methods: A total of 1401 patients were enrolled, with 852 (60.8%) patients receiving 5 000 000 U of IFN-α-2b via aerosol inhalation twice daily. The primary outcome was a composite measure consisting of mechanical ventilation, intensive care unit (ICU) admission and death. A subgroup analysis was performed to investigate the impact of the IFN-α-2b initiation schedule on symptom onset., Results: The risk probability for crude endpoints was lower in the IFN-α-2b group (3.8%) than in the non-IFN-α-2b group (9.3%, P < .001). After adjusting the confounding factors, IFN-α-2b therapy achieved a reduction of 64% in occurrence of endpoint events (hazard ratio, 0.36; 95% confidence interval [CI], 0.21-0.62). In the subgroup analysis, compared with patients who received IFN-α-2b treatment 0-2 days after symptom onset, the hazard ratio for endpoints was 2.2 (95% CI, 0.43-11.13) in patients who received the therapy 3-5 days after symptom onset, 5.89 (95% CI, 0.99-35.05) in patients who received the therapy 6-8 days after symptom onset, and remained at a high level thereafter., Conclusions: IFN-α-2b aerosol inhalation therapy may be associated with improved clinical outcomes in patients with COVID-19, and delayed IFN-α-2b intervention was associated with increased probabilities of risk events. Further randomized clinical trials are needed to validate the preliminary findings of this study., (© 2021 British Pharmacological Society.)

Background Chest compression (CC) during sustained inflations (CC+SI) compared with CC with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation in asphyxiated pediatric piglets will reduce time to return of spontaneous circulation (ROSC). Methods and Results Piglets (20-23 days of age, weighing 6.2-10.2 kg) were anesthetized, intubated, instrumented, and exposed to asphyxia. Cardiac arrest was defined as mean arterial blood pressure <25 mm Hg with bradycardia. After cardiac arrest, piglets were randomized to CC+SI (n=12) or CCaV (n=12) or sham (n=8). Sham-operated animals had no asphyxia. Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded. There were no differences in baseline parameters or the duration and degree of asphyxiation. Median (interquartile range) Time to ROSC was 248 (41-346) seconds compared with 720 (167-720) seconds in the CC+SI group and CCaV group, respectively ( P =0.0292). There was a 100% higher rate of ROSC in the CC+SI group versus CCaV group, with 10 (83%) versus 5 (42%) achieving ROSC ( P =0.089), respectively. Piglets in the CC+SI and CCaV groups received intravenous epinephrine boluses to achieve ROSC (8/12 versus 10/12 P =0.639). There was a significantly higher minute ventilation in the CC+SI group, which was secondary to a 5-fold increase in the number of inflations per minute and a 1.5-fold increase in tidal volume. Conclusions CC+SI reduced time to ROSC and improved survival compared with using CCaV. CC+SI allowed passive ventilation of the lung while providing chest compressions. This technique warrants further studies to examine the potential to improve outcomes in pediatric patients with cardiac arrest. Registration URL: https://www.preclinicaltrials.eu; Unique identifier: PCTE0000152.

New Findings: What is the central question of the study? Does respiratory support ensure blood gas homeostasis and the relevance of experimental outcomes? What is the main finding and its importance? Spontaneous breathing during surgical intervention under anaesthesia results in impaired gas exchange and loss of diaphragm muscle strength in rats. Subsequent short-term mechanical ventilation restored blood gas homeostasis and diaphragm muscle strength. Blood gas homeostasis interferes substantially with experimental conditions and may alter study results. Monitoring and maintenance of blood gas balance is required to ensure quality and relevance of physiological animal experiments., Abstract: In pre-clinical small animal studies with surgical interventions under general anaesthesia, animals are often left to breathe spontaneously. However, anaesthesia may impair respiratory functions and result in disturbed blood gas homeostasis. In turn, the disturbed blood gas homeostasis can affect physiological functions and thus unintentionally impact the experimental results. We hypothesized that short-term mechanical ventilation restores blood gas balance and physiological functions despite anaesthesia and surgical interventions. Therefore, we investigated variables of blood gas analyses and diaphragm muscle strength in rats anaesthetized with ketamine/medetomidine after tracheotomy and catheterization of the carotid artery under spontaneous breathing and after 20 min of mechanical ventilation following the same surgical intervention. Spontaneous breathing during general anaesthesia and surgical intervention resulted in unphysiological blood oxygen partial pressure (<65 mmHg) and carbon dioxide partial pressure (>55 mmHg). After subsequent short-term mechanical ventilation, blood gas partial pressures were restored to their physiological ranges. Additionally, diaphragm muscle strength of animals breathing spontaneously was lower compared to animals that received subsequent mechanical ventilation (P = 0.0063). We conclude that spontaneous breathing of rats under ketamine/medetomidine anaesthesia is not sufficient to maintain a physiological blood gas balance. Disturbed blood gas balance is related to reduced diaphragm muscle strength. Mechanical ventilation for only 20 min restores blood gas homeostasis and muscle strength. Therefore, monitoring and maintenance of blood gas balance should be conducted to ensure quality and relevance of small animal experiments., (© 2020 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Coagulopathy causes morbidity and mortality in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Yet, the mechanisms are unclear and biomarkers are limited. Early in the pandemic, we observed markedly elevated factor V activity in a patient with COVID-19, which led us to measure factor V, VIII, and X activity in a cohort of 102 consecutive inpatients with COVID-19. Contemporaneous SARS-CoV-2-negative controls (n = 17) and historical pre-pandemic controls (n = 260-478) were also analyzed. This cohort represents severe COVID-19 with high rates of ventilator use (92%), line clots (47%), deep vein thrombosis or pulmonary embolism (DVT/PE) (23%), and mortality (22%). Factor V activity was significantly elevated in COVID-19 (median 150 IU/dL, range 34-248 IU/dL) compared to contemporaneous controls (median 105 IU/dL, range 22-161 IU/dL) (P < .001)-the strongest association with COVID-19 of any parameter studied, including factor VIII, fibrinogen, and D-dimer. Patients with COVID-19 and factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49, 33%) compared to those with factor V activity ≤150 IU/dL (7/53, 13%) (P = .03). Within this severe COVID-19 cohort, factor V activity associated with SARS-CoV-2 load in a sex-dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality. Together, these data reveal marked perturbations of factor V activity in severe COVID-19, provide links to SARS-CoV-2 disease biology and clinical outcomes, and nominate a candidate biomarker to investigate for guiding anticoagulation therapy in COVID-19., (© 2020 Wiley Periodicals LLC.)

Background Alterations in serum creatinine levels delay the identification of severe cardiac surgery-associated acute kidney injury. To provide timely diagnosis, novel predictive tools should be investigated. Methods and Results This prospective observational study consists of a screening cohort (n=204) and a validation cohort (n=198) from 2 centers from our hospital. Thirty-two inflammatory cytokines were measured via a multiplex cytokine assay. Least absolute shrinkage and selection operator regression was conducted to select the cytokine signatures of severe cardiac surgery-associated acute kidney injury. Afterwards, the significant candidates including interferon-γ, interleukin-16, and MIP-1α (macrophage inflammatory protein-1 alpha) were integrated into the logistic regression model to construct a predictive model. The predictive accuracy of the model was evaluated in these 2 cohorts. The cytokine-based model yielded decent performance in both the screening (C-statistic: 0.87, Brier 0.10) and validation cohorts (C-statistic: 0.86, Brier 0.11). Decision curve analysis revealed that the cytokine-based model had a superior net benefit over both the clinical factor-based model and the established plasma biomarker-based model for predicting severe acute kidney injury. In addition, elevated concentrations of each cytokine were associated with longer mechanical ventilation times, intensive care unit stays, and hospital stays. They strongly predicted the risk of composite events (defined as treatment with renal replacement therapy and/or in-hospital death) (OR of the fourth versus the first quartile [95% CI]: interferon-γ, 27.78 [3.61-213.84], interleukin-16, 38.07 [4.98-291.07], and MIP-1α, 9.13 [2.84-29.33]). Conclusions Our study developed and validated a promising blood cytokine-based model for predicting severe acute kidney injury after cardiac surgery and identified prognostic biomarkers for assisting in outcome risk stratification.

Background Palliative care supports quality of life, symptom control, and goal setting in heart failure (HF) patients. Unlike hospice, palliative care does not restrict life-prolonging therapy. This study examined the association between palliative care during hospitalization for HF on the subsequent transitions and procedures. Methods and Results Veterans admitted to hospitals with HF from 2010 to 2015 were randomly selected for the Veterans Administration External Peer Review Program. Variables pertaining to demographic, clinical, laboratory, and usage were captured from Veterans Administration electronic records. Patients receiving hospice services before admission were excluded. Patients who received palliative care were propensity matched to those who did not. The primary outcomes were whether the patient experienced transitions or procedures in the 6 months after admission. Transitions included multiple readmissions (≥2) or intensive care admissions and procedures included mechanical ventilation, pacemaker implantation, or defibrillator implantation. Among 57 182 hospitalized HF patients, 1431 received palliative care, and were well matched to 1431 without (standardized mean differences ≤ ±0.05 on all matched variables). Palliative care was associated with significantly fewer multiple rehospitalizations (30.9% versus 40.3%, P <0.001), mechanical ventilation (2.8% versus 5.4%, P =0.004), and defibrillator implantation (2.1% versus 3.6%, P =0.01). After adjustment for facility fixed effects, palliative care consultation was associated with a significantly reduced hazard of multiple readmissions (adjusted hazard ratio=0.73, 95% CI, 0.64-0.84) and mechanical ventilation (adjusted hazard ratio=0.76, 95% CI, 0.67-0.87). Conclusions Palliative care during HF admissions was associated with fewer readmissions and less mechanical ventilation. When available, engagement of HF patients and caregivers in palliative care for symptom control, quality of life, and goals of care discussions may be associated with reduced rehospitalizations and mechanical ventilation.

Background Packed red blood cell transfusion may improve oxygen content in single-ventricle neonates, but its effect on clinical outcomes after Stage 1 palliation is unknown. Methods and Results Retrospective multicenter analysis of packed red blood cell transfusion exposures in neonates after Stage 1 palliation, excluding those with intraoperative mortality or need for extracorporeal membrane oxygenation. Transfusion practice variability was assessed, and multivariable regression used to identify transfusion risk factors. After propensity score adjustment for severity of illness, clinical outcomes were compared between transfused and nontransfused subjects. Of 396 subjects, 323 (82%) received 930 postoperative red blood cell transfusions. Packed red blood cell volume (median 9-42 mL/kg [ P <0.0001]), donor exposures (1-2 [ P <0.0001]), transfusion number (1-3 [ P <0.0001]), and pretransfusion hemoglobin (12.1-13 g/dL, P =0.0049) varied between sites. Cyanosis ( P =0.02), chest tube output ( P =0.0003), and delayed sternal closure ( P =0.0033) increased transfusion risk. Transfusion was associated with prolonged mechanical ventilation (6 [interquartile range 4, 12] versus 3 [1, 5] days, P =0.02) and intensive care unit stay (19 [12, 33] versus 9 [6, 19] days, P =0.016). When stratified by number of transfusions (0, 1, or >1), duration of mechanical ventilation (3 [1, 5] versus 4 [3, 6] versus 9 [5, 16] days [ P <0.0001]) and intensive care unit stay (9 [6, 19] versus 13 [8, 25] versus 21 [13, 38] days [ P <0.0001]) increased for those transfused more than once. Most subjects who died were transfused, though the association with mortality was not significant. Conclusions Packed red blood cell transfusion after Stage 1 palliation is common, and transfusion practice is variable. Transfusion is a significant predictor of longer intensive care unit stay and mechanical ventilation. Further studies to define evidence-based transfusion thresholds are warranted.

Neonatal chronic lung disease (nCLD) affects a significant number of neonates receiving mechanical ventilation with oxygen-rich gas (MV-O 2 ). Regardless, the primary molecular driver of the disease remains elusive. We discover significant enrichment for SNPs in the PDGF-Rα gene in preterms with nCLD and directly test the effect of PDGF-Rα haploinsufficiency on the development of nCLD using a preclinical mouse model of MV-O 2 In the context of MV-O 2 , attenuated PDGF signaling independently contributes to defective septation and endothelial cell apoptosis stemming from a PDGF-Rα-dependent reduction in lung VEGF-A. TGF-β contributes to the PDGF-Rα-dependent decrease in myofibroblast function. Remarkably, endotracheal treatment with exogenous PDGF-A rescues both the lung defects in haploinsufficient mice undergoing MV-O 2 Overall, our results establish attenuated PDGF signaling as an important driver of nCLD pathology with provision of PDGF-A as a protective strategy for newborns undergoing MV-O 2 ., (© 2017 Helmholtz Zentrum München Published under the terms of the CC BY 4.0 license.)

Aims: Codeine containing analgesics are commonly taken in overdose, but the frequency of respiratory depression is unknown. We investigated whether paracetamol-codeine combination overdoses caused respiratory depression more than paracetamol alone., Methods: We reviewed deliberate self-poisoning admissions with paracetamol (>2 g) and paracetamol-codeine combinations presenting to a tertiary toxicology unit (1987-2013). Demographic information, clinical effects, treatment (naloxone, length of stay [LOS], mechanical ventilation) were extracted from a prospective database. Primary outcome was naloxone requirement or ventilation for respiratory depression., Results: From 4488 presentations, 1376 admissions were included with paracetamol alone (929), paracetamol-codeine combinations (346) or paracetamol-codeine-doxylamine combinations (101) without co-ingestants. Median age was 23 years (12-89 years); 1002 (73%) were female. Median dose was 12 g (interquartile range [IQR]: 7.5-20 g). Median LOS was 16 h (IQR: 6.5-27 h) and 564 (41%) were given acetylcysteine. Significantly larger paracetamol doses were ingested and more acetylcysteine given in paracetamol alone versus paracetamol combination overdoses. Seven out of 1376 patients were intubated or received naloxone (0.5%; 95% CI: 0.2-1.1%), three intubated, three given naloxone and one both. Three out of 929 patients ingesting paracetamol alone (0.3%; 95% CI: 0.1-1%) required intubation or naloxone, compared to two out of 346 ingesting paracetamol-codeine combinations (0.6%; 95% CI: 0.1-2.3%; absolute difference, 0.26%; 95% CI: -0.7-1.2%; P = 0.62). Two out of 101 patients ingesting paracetamol-codeine-doxylamine combinations (2%; 95% CI: 0.3-8%) required intubation or naloxone. Four patients were intubated for reasons other than respiratory depression: hepatotoxicity (2), retrieval (1), no data (1). Two out of 929 (0.2%) paracetamol alone overdoses had a Glasgow coma score < 9 compared to three out of 346 (0.9%) in the paracetamol-codeine group., Conclusions: Paracetamol-codeine combination overdoses are rarely associated with severe respiratory depression, with only two given naloxone and none intubated for respiratory depression., (© 2016 The British Pharmacological Society.)

Background: Atrial fibrillation (AF) is a common cause for hospitalization, but there are limited data regarding acute kidney injury requiring dialysis (AKI-D) in AF hospitalizations. We aimed to assess temporal trends and outcomes in AF hospitalizations complicated by AKI-D utilizing a nationally representative database., Methods and Results: Utilizing the Nationwide Inpatient Sample, AF hospitalizations and AKI-D were identified using diagnostic and procedure codes. Trends were analyzed overall and within subgroups and utilized multivariable logistic regression to generate adjusted odds ratios (aOR) for predictors and outcomes including mortality and adverse discharge. Between 2003 and 2012, 3751 (0.11%) of 3 497 677 AF hospitalizations were complicated by AKI-D. The trend increased from 0.3/1000 hospitalizations in 2003 to 1.5/1000 hospitalizations in 2012, with higher increases in males and black patients. Temporal changes in demographics and comorbidities explained a substantial proportion but not the entire trend. Significant comorbidities associated with AKI-D included mechanical ventilation (aOR 13.12; 95% CI 9.88-17.43); sepsis (aOR 8.20; 95% CI 6.00-11.20); and liver failure (aOR 3.72; 95% CI 2.92-4.75). AKI-D was associated with higher risk of in-hospital mortality (aOR 3.54; 95% CI 2.81-4.47) and adverse discharge (aOR 4.01; 95% CI 3.12-5.17). Although percentage mortality within AKI-D decreased over the decade, attributable risk percentage mortality remained stable., Conclusions: AF hospitalizations complicated by AKI-D have quintupled over the last decade with differential increase by demographic groups. AKI-D is associated with significant morbidity and mortality. Without effective AKI-D therapies, focus should be on early risk stratification and prevention to avoid this devastating complication., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background: Percutaneous closure of patent ductus arteriosus (PDA) in term neonates is established, but data regarding outcomes in infants born very preterm (<32 weeks of gestation) are minimal, and no published criteria exist establishing a minimal weight of 4 kg as a suitable cutoff. We sought to analyze outcomes of percutaneous PDA occlusion in infants born very preterm and referred for PDA closure at weights <4 kg., Methods and Results: Retrospective analysis (January 2005-January 2014) was done at a single pediatric center. Procedural successes and adverse events were recorded. Markers of respiratory status (need for mechanical ventilation) were determined, with comparisons made before and after catheterization. A total of 52 very preterm infants with a median procedural weight of 2.9 kg (range 1.2-3.9 kg) underwent attempted PDA closure. Twenty-five percent (13/52) of infants were <2.5 kg. Successful device placement was achieved in 46/52 (88%) of infants. An adverse event occurred in 33% of cases, with an acute arterial injury the most common complication. We observed no association between weight at time of procedure and the risk of an adverse event. No deaths were attributable to the PDA closure. Compared to precatheterization trends, percutaneous PDA closure resulted in improved respiratory status, including less exposure to mechanical ventilation (mixed effects logistic model, P<0.01)., Conclusions: Among infants born very preterm, percutaneous PDA closure at weights <4 kg is generally safe and may improve respiratory health, but risk of arterial injury is noteworthy. Randomized clinical trials are needed to assess clinically relevant differences in outcomes following percutaneous PDA closure versus alternative (surgical ligation) management strategies., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)